L-methionine

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May - June 1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: males 38 days, female 42 days
- Weight at study initiation: 100 - 106 g
- Fasting period before study: 15 - 16 h before application of test material
- Housing: individually
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24°C +/- 0.5°C
- Humidity (%): 60% +/- 3%

Route of administration:

oral: gavage

Vehicle:

other: carboxy äthylcellulose gel 1%

Details on oral exposure:

VOLUME APPLIED: 25 mL/kg b.w.

Doses:

6.35, 7.90 and 10.0 g/kg b.w.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 4 weeks

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality occured

Clinical signs:

other: no clinical signs observed

Gross pathology:

no effects observed

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

In a well documented non-GLP study (73-0018-DKT) similar to OECD Guideline 401 the LD50 in Sprague-Dawley rats was reported to be >10000 mg/kg bw.

This result was confirmed in another non-GLP study (73-0022-DKT) with exactly the same LD50 (>10000 mg/kg bw).

The low oral toxicity was further confirmed in a GLP guideline study according to the National Standard of the People's Republic of China (2011-0320-DGT) performed with the read-across substance D,L-methionine. In this study a single oral administration of 5610 mg D,L-methionine/kg b.w. did not reveal any signs of toxicity.

 

Acute inhalation toxicity

No data on acute inhalation toxicity for L-methionine is available. Significant exposure of humans via inhalation is unlikely taking into account the vapour pressure and the particle size of the substance, while exposure of humans via skin contact is likely.

However, there is an in vivo OECD 403 GLP-guideline study (2003 -0590 -DGT) available for the substance D,L-methionine.Read-across of the D,L-methionine study to L-methionine was used due to structural similarities and the physico-chemical similarities of the enantiomers according to Reach regulation (Annex XI, 1.5). Further, L-methionine is present in a considerable amount in racemic methionine (approximatly 50%).The aim of the available limit test with D,L-methionine was to obtain information on the acute inhalative toxicity following a single 4 hour exposure of rats. No signs of toxicity were observed at 5.25 mg test substance/L air.

 

Acute dermal toxicity

No data on acute dermal toxicity for L-methionine is available. The substance is of very low acute systemic toxicity (LD50 in acute oral toxicity studies > 10000 mg/kg bw). Due to this very low toxicity and the fact that L-methionine with high water solubility and a log P value well below 0 may be too hydrophilic to cross the lipid rich environment of the stratum corneum it is highly improbable that an acute dermal toxicity study would result in any toxicity. Therefore and for animal welfare reasons no further acute dermal toxicity study is justified and the dermal LD50 is assumed to be > 2000 mg/kg bw.